Intramolecular C-H Insertion Reactions of Diazoacetates
J. Am. Chem. Soc., Vol. 118, No. 37, 1996 8845
NMR δ 176.7, 84.0, 45.0, 38.2, 33.0, 25.5, 21.9, 20.8, 19.8; IR (film)
1783 cm-1; mass spectrum, m/z (relative abundance) 154 (M, 6), 108
(11), 95 (18), 93 (16), 82 (100), 81 (17), 70 (14), 69 (23), 68 (13), 67
(34), 56 (21), 55 (28). Anal. Calcd for C9H14O2: C, 70.10; H, 9.15.
Found: C, 70.16; H, 9.12.
resulting light brown-orange-colored solution was stirred at room
temperature for 24 h, after which methanesulfonyl azide (2.32 g, 0.0192
mol) and triethylamine (2.67 mL, 0.0192 mol) were added, and stirring
was continued overnight. A solution of lithium hydroxide (1.38 g,
0.0576 mol) in 20 mL of water was then added, and the dark brown
solution was stirred for an additional 6 h. The aqueous THF solution
was extracted three times with 50-mL portions of ether, and the
combined ether solution was washed three times with 50-mL portions
of water and brine before drying over anhydrous MgSO4. The solvent
was removed under reduced pressure, and the residue was purified by
column chromatography on silica gel (10:1 hexanes/ethyl acetate) to
(1R,5S,9S)-9-Methyl-2-oxabicyclo[4.3.0]nonan-3-one, (1S)-14: col-
orless liquid; Rf ) 0.29 (5:1 hexanes/EtOAc); [R]20 ) +134.5° (c
D
1
0.40, CHCl3) for >99% ee; H NMR δ 3.44 (t, J ) 10.4 Hz, 1 H),
2.52 (dd, J ) 16.1, 6.2 Hz, 1 H), 2.23 (dd, J ) 16.1, 13.0 Hz, 1 H),
2.05-1.69 (comp, 5 H), 1.47-1.00 (comp, 3 H), 1.06 (d, J ) 6.2 Hz,
3 H); 13C NMR δ 176.6, 90.7, 44.2, 36.7, 36.1, 33.3, 28.2, 25.3, 18.5;
IR (film) 1788 cm-1; mass spectrum, m/z (relative abundance) 154 (M,
1), 97 (13), 95 (13), 82 (100), 81 (20), 68 (26), 67 (39), 55 (43), 54
(29). Anal. Calcd for C9H14O2: C, 70.10; H, 9.15. Found: C, 70.18;
H, 9.21.
provide 2.70 g of a yellow oil identified as 28 (75% yield): [R]22
)
D
+ 26.6 (c 1.04, CHCl3); 1H NMR δ 5.28 (br s, 1 H), 4.72 (br s, 1 H),
1.97 (dq, J ) 14.4, 3.2Hz, 1 H), 1.80-1.22 (comp, 5 H), 1.12-0.90
(comp, 3 H), 0.89 (d, J ) 5.9 Hz, 6 H), 0.86 (d, J ) 6.7 Hz, 3 H); 13
C
NMR δ 165.9, 71.7, 46.8, 46.1, 39.3, 34.7, 29.2, 26.4, 24.9, 22.1, 20.8,
20.7; IR (CHCl3) 2113 (CdN2), 1685 (CdO) cm-1. Anal. Calcd for
C12H20N2O2: C, 64.26; H, 8.98; N, 12.49. Found: C, 64.17; H, 9.09;
N, 12.93.
Catalytic diazo decomposition of (+)-neomenthyl diazoacetate
(28) was performed by the same procedure as described for 6.
Diastereoisomer and regioisomer separations were performed by GC
with baseline resolution on a 30-m methyl phenyl silicone column.
Spirolactone 31 was not stable to GC analysis.
(1R,5R,9S)-9-Methyl-2-oxabicyclo[4.3.0]nonan-3-one, (1S)-15: col-
orless liquid; Rf ) 0.24 (5:1 hexanes/EtOAc); [R]20D ) -33.5° (c 0.71,
CHCl3); 1H NMR δ 4.09 (dd, J ) 7.6, 6.5 Hz, 1 H), 2.72-2.60 (m, 1
H), 2.43 (d, J ) 16.6 Hz, 1 H), 2.36 (dd, J ) 16.6, 1.8 Hz, 1 H),
1.74-1.34 (comp, 7 H), 1.05 (d, J ) 6.6 Hz, 3 H); 13C NMR δ 177.2,
85.2, 34.2, 33.4, 33.3, 29.7, 25.9, 19.4, 18.4; IR (film) 1788 cm-1
;
mass spectrum, m/z (relative abundance) 154 (M, 5), 126 (32), 98 (26),
97 (47), 95 (46), 94 (64), 82 (78), 68 (42), 67 (42), 56 (24), 55 (100).
Anal. Calcd for C9H14O2: C, 70.10; H, 9.15. Found: C, 70.04; H,
9.06.
(1S,5R,6R,9S)-9-Isopropyl-6-methyl-2-oxabicyclo[4.3.0]nonan-3-
1
one, 29: colorless liquid; [R]22 ) +44.0° (c 1.02, CHCl3); H NMR
(1R,5S)-5-Methyl-1-oxaspiro[5.3]nonan-2-one, (1S)-16: colorless
D
1
δ 4.57 (t, J ) 3.7 Hz, 1 H), 2.62 (dd, J ) 16.8, 6.6 Hz, 1 H), 2.35 (d,
J ) 16.8 Hz, 1 H), 1.86-1.68 (comp, 4 H), 1.28-1.08 (comp, 3 H),
0.94-0.85 (m, 1 H), 0.99 (d, J ) 6.7 Hz, 3 H), 0.95 (d, J ) 6.7 Hz,
3 H), 0.93 (d, J ) 6.4 Hz, 3 H); 13C NMR δ 177.8, 81.1, 45.8, 43.6,
liquid; Rf ) 0.32 (5:1 hexanes/EtOAc); H NMR δ 3.19 (d, J ) 16.2
Hz, 1 H), 2.88 (d, J ) 16.2 Hz, 1 H), 2.05-1.76 (comp, 5 H), 1.69-
1.55 (m, 1 H), 1.42-1.25 (comp, 2 H), 1.16-1.05 (m, 1 H), 1.01 (d,
J ) 6.8 Hz, 3 H); 13C NMR δ 168.6, 81.5, 42.1, 37.7, 35.9, 31.6, 24.0,
23.6, 14.2; IR (film) 1821 cm-1; mass spectrum, m/z (relative
abundance) 154 (M, not observed), 112 (61), 110 (32), 95 (48), 84
(36), 82 (22), 81 (46), 69 (50), 68 (100), 67 (64), 56 (35), 55 (57), 54
(15), 53 (20).
36.8, 33.0, 32.0, 29.7, 23.8, 21.0, 20.6, 20.0; IR (CHCl3) 1767 cm-1
.
Anal. Calcd for C12H20O2: C, 73.43; H, 10.27. Found: C, 73.51; H,
10.35.
(1S,6S,9R)-5,5,9-Trimethyl-2-oxabicyclo[4.4.0]decan-3-one, 30:
colorless liquid; [R]22D ) -48.6° (c 1.10, CHCl3); 1H NMR δ 4.72 (q,
J ) 2.5 Hz, 1 H), 2.33 (d, J ) 18.1 Hz, 1 H), 2.24 (d, J ) 18.1 Hz,
1 H), 2.09 (dq, J ) 14.4, 3.3 Hz, 1 H), 1.81-1.59 (comp, 3 H), 1.37-
1.09 (comp, 3 H), 0.98-0.90 (m, 1 H), 1.12 (s, 3 H), 0.99 (s, 3 H),
0.88 (d, J ) 6.6 Hz, 3 H); 13C NMR δ 172.3, 76.1, 43.0, 40.6, 39.4,
33.8, 32.3, 29.3, 27.2, 25.6, 22.0, 21.8; IR (CHCl3) 1717 cm-1. Anal.
Calcd for C12H20O2: C, 73.43; H, 10.27. Found: C, 73.30; H, 10.38.
(1S,5S,8R)-5-Isopropyl-8-methyl-1-oxaspiro[5.3]nonan-2-one, 31:
colorless liquid; [R]22D ) -4.56° (c 1.03, CHCl3); 1H NMR δ 3.52 (d,
J ) 16.4 Hz, 1 H), 2.87 (d, J ) 16.4 Hz, 1 H), 2.17-1.36 (comp, 9
H), 0.98 (d, J ) 6.8 Hz, 3 H), 0.92 (d, J ) 6.8 Hz, 3 H), 0.90 (d, J )
6.9 Hz, 3 H); 13C NMR 168.6, 81.7, 47.0, 46.8, 44.9, 34.3, 29.1, 26.2,
Catalytic diazo decomposition of l-(-)- and d-(+)-menthyl
diazoacetates was performed by the same procedure as described for
6 except that the catalyst was dissolved in 10-12 mL of anhydrous
CH2Cl2. Diastereoisomer and regioisomer separations were performed
by GC with baseline resolution on a 30-m methyl phenyl silicone
column. Spirolactones 20 and 27 were not stable to GC analysis.
Reaction products were isolated by column chromatography on silica
gel (5:1 hexanes/ethyl acetate); the order of elution was â-lactone,
γ-lactone, and δ-lactone.
(1R,5R,6R,9S)-9-Isopropyl-6-methyl-2-oxabicyclo[4.3.0]nonan-3-
one, 18: white solid; mp 67-69 °C; [R]22D ) +132.8° (c 1.05, CHCl3);
1H NMR δ 3.70 (t, J ) 10.5 Hz, 1 H), 2.54 (dd, J ) 16.2, 6.4 Hz, 1
H), 2.18 (dd, J ) 16.2, 13.2 Hz, 1 H), 1.99-1.88 (m, 1 H), 1.82-1.56
(comp, 4 H), 1.53-1.38 (m, 1 H), 1.26-0.98 (comp, 2 H), 0.94 (d, J
) 6.8 Hz, 6 H), 0.89 (d, J ) 6.9 Hz, 3 H); 13C NMR δ 176.7, 86.3,
51.2, 46.7, 35.0, 34.6, 34.4, 28.5, 25.0, 19.8, 19.7, 17.8; IR (CHCl3)
1769 cm-1. Anal. Calcd for C12H20O2: C, 73.43; H, 10.27. Found:
C, 73.29; H, 10.34.
(1S,6R,9S)-5,5,9-Trimethyl-2-oxabicyclo[4.4.0]decan-3-one, 26:
white solid; mp 40-42 °C; [R]22D ) -10.6° (c 0.96, CHCl3); 1H NMR
δ 4.07 (dt, J ) 4.2, 11.0, 1 H), 2.42 (d, J ) 17.1 Hz, 1 H), 2.28 (d, J
) 17.1 Hz, 1 H), 2.14 (dtd, J ) 12.2, 3.8, 2.0 Hz, 1 H), 1.85 (dq, J )
12.4, 3.1 Hz, 1 H), 1.79-1.72 (m, 1 H), 1.60-1.44 (m, 1 H), 1.33-
0.89 (comp, 4 H), 0.99 (s, 3 H), 0.97 (d, J ) 6.6 Hz, 3 H), 0.95 (s, 3
H); 13C NMR δ 171.3, 79.7, 48.2, 46.2, 41.2, 34.2, 31.8, 31.3, 28.4,
23.9, 21.9, 21.7; IR (CHCl3) 1721 cm-1. Anal. Calcd for C12H20O2:
C, 73.43; H, 10.27. Found: C, 73.36; H, 10.25.
23.4, 21.8, 21.6, 18.3; IR (CHCl3) 1813 cm-1
. Anal. Calcd for
C12H20O2: C, 73.43; H, 10.27. Found: C, 73.36; H, 10.35.
2-Octyl Diazoacetates 32. To a solution of (R)-2-octanol (4.59 g,
35.3 mmol) and triethylamine (0.18 g, 1.8 mmol) in 50 mL of dry
THF cooled at 0 °C was added diketene (4.45 g, 53.0 mmol) over 30
min. The resulting solution was stirred for 1 h at 0 °C and then for 12
h at room temperature, after which the solvent was evaporated under
reduced pressure, and the crude product was diluted with ether (100
mL), passed through a short plug of silica gel, and then distilled under
reduced pressure (bp 116-119 °C at 0.6 Torr) to afford 7.28 g of a
colorless liquid identified as 2-octyl acetoacetate (50.9 mmol, 96%
yield): 1H NMR δ 4.96 (sex, J ) 6.2 Hz, 1 H), 3.43 (s, 2 H), 2.27 (s,
3 H), 1.70-1.53 (m, 1 H), 1.52-1.42 (m, 1 H), 1.40-1.20 (m, 8 H),
1.24 (d, J ) 6.2 Hz, 3 H), 0.88 (t, J ) 6.4 Hz, 3 H); enol form at 5.02
(s, 1 H). 1.94 (s, 3 H); 13C NMR δ 200.7, 166.8, 72.4, 50.5, 35.8,
31.7, 30.1, 29.1, 25.3, 22.6, 19.8, 14.0.
To a solution of the acetoacetate ester (3.58 g, 16.7 mmol) in dry
acetonitrile (30 mL) were added triethylamine (1.69 g, 16.7 mmol) and
then methanesulfonyl azide (2.43 g, 20.1 mmol). The resulting solution
was stirred for 4 h at room temperature, and then LiOH‚H2O (2.11 g,
50.2 mmol) in 43 mL of H2O (5% in H2O) was added. This mixture
was stirred for 5 h and then diluted with H2O (200 mL) and extracted
three times with 50-mL portions of ether. The combined ether extract
was washed twice with 150-mL portions of water and once with 150
mL of brine and then dried over anhydrous MgSO4, and the solvent
was removed under reduced pressure. The crude diazo ester was passed
5-Isopropyl-8-methyl-1-oxaspiro[5.3]nonan-2-ones 20 and 27 from
reactions of 17 with Rh2(4(R)-MEOX)4 or of 24 with Rh2(4(S)-MEOX)4
underwent decomposition in attempted chromatographic purifications.
Their presence, however, was confirmed in reaction mixtures by
1
characteristic H NMR absorptions at δ 3.33 (dd, J ) 16.3, 1.4 Hz, 1
H) and 2.91 (d, J ) 16.3 Hz, 1 H). The carbonyl absorption in the IR
at 1814 cm-1 confirmed the â-lactone ring.
(1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl Diazoacetate, 28.
Diketene (1.1 mL, 0.019 mol) was added over 10 min to an ice bath-
cooled solution of (+)-neomenthol (2.61 g, 0.0167 mol) and trieth-
ylamine (0.22 mL, 1.6 mmol) in 25 mL of anhydrous THF. The